Abstract
Although smallpox has been known for centuries, the oldest available variola virus strains were isolated in the early 1940s. At that time, large regions of the world were already smallpox-free. Therefore, genetic information of these strains can represent only the very last fraction of a long evolutionary process. Based on the genomes of 48 strains, two clades are differentiated: Clade 1 includes variants of variola major, and clade 2 includes West African and variola minor (Alastrim) strains. Recently, the genome of an almost 400-year-old Lithuanian mummy was determined, which fell basal to all currently sequenced strains of variola virus on phylogenetic trees. Here, we determined two complete variola virus genomes from human tissues kept in a museum in Prague dating back 60 and 160 years, respectively. Moreover, mass spectrometry-based proteomic, chemical, and microscopic examinations were performed. The 60-year-old specimen was most likely an importation from India, a country with endemic smallpox at that time. The genome of the 160-year-old specimen is related to clade 2 West African and variola minor strains. This sequence likely represents a new endemic European variant of variola virus circulating in the midst of the 19th century in Europe.
Highlights
IntroductionSmallpox is caused by variola virus (VARV), which belongs to the genus Orthopoxvirus of the family
Smallpox is caused by variola virus (VARV), which belongs to the genus Orthopoxvirus of the familyPoxviridae
Permission to perform the work reported was granted by ACVVR, and we analyzed these samples under maximum safety precautions and in accordance with locally agreed national guidelines
Summary
Smallpox is caused by variola virus (VARV), which belongs to the genus Orthopoxvirus of the family. West African VARVs share a relatively recent common ancestor with Alastrim minor. VARVs cluster according to their geographical origin [4]. This is not surprising, since smallpox is transmitted via close human-to-human contact, which results in a rather slow spread. Research teams, using archival data on smallpox outbreaks combined with phylogenetic analyses, have obtained contradictory results on the possible time of VARV emergence [5,6,7] based on the method used. Smallpox became endemic in West Africa in the 14th century AD and started to diverge in this geographically isolated region. 300–400 YBP, the West African VARV variant imported to South America started to evolve into the South American VARV Alastrim subtype.
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